This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent work (Mathur et al., 2008) on a new, higher sensitivity preamplifier design for Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) revealed a number of artifact peaks (spectral features) which do not contain useful chemical information. In order to determine the cause of these artifacts and eliminate them, these severely distorted spectra were compared with similarly distorted signal models (Mathur et al., 2009). C60 was chosen as the compound of interest, whose mass spectra were obtained using the custom built 7T MALDI FT-ICR mass spectrometer. Simulated spectra were generated using a MATLAB script. Three undamped sinusoidal functions were used to model the first three isotopes of C60. It was found that imbalance in the gain or bias of the amplifier could lead to overloading of the analogue to digital converter (ADC) which resulted in appearance of harmonics in the mass spectra. This observation was confirmed by simulation, where clipping of one side of the digital transient led to appearance of multiple harmonics peaks in the simulated spectra. Fold-over peaks due to under-sampling (aliasing) were also apparent for higher order harmonics peaks. It was further shown that severe overloading of the ADC (even when the amplifier is perfectly balanced with no DC offsets) could also cause distortion in the isotopic distribution of ions, which would make the automatic interpretation of the mass spectra difficult. Finally, radio-frequency interference (RFI) noise riding on the ICR signal causing imbalance and/or overloading of the ADC may also induce intermodulations between isotopic peaks and the RFI noise, leading to undesirable artifacts. Thus, the source of several common signal processing artifacts was thereby determined and correlated to RFI noise and saturation of the amplifier and/or the digitizer. Under such conditions, the fast Fourier transform (FFT) generates spectral artifact peaks corresponding to harmonics and mixing frequencies of the real signal peaks and RFI frequencies. While this study was done using the FT-ICR MS data, it is important to stress that these artifacts are inherent to the digitization and FFT process and thus are relevant to any FT-based MS instrument, including the orbitrap and FT ion trap.